[HTML][HTML] Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Rα

S Viaud, M Terme, C Flament, J Taieb, F André… - PloS one, 2009 - journals.plos.org
S Viaud, M Terme, C Flament, J Taieb, F André, S Novault, B Escudier, C Robert…
PloS one, 2009journals.plos.org
Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional
MHC/peptide complexes promoting T cell-dependent tumor rejection. In the first Phase I trial
using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell
responses prompted the search for alternate effector mechanisms. Mouse studies unraveled
the bioactivity of Dex on NK cells. Indeed, Dex promoted an IL-15Rα-and NKG2D-
dependent NK cell proliferation and activation respectively, resulting in anti-metastatic …
Dendritic cell (DC) derived-exosomes (Dex) are nanomeric vesicles harboring functional MHC/peptide complexes promoting T cell-dependent tumor rejection. In the first Phase I trial using peptide-pulsed Dex, the observation of clinical regressions in the absence of T cell responses prompted the search for alternate effector mechanisms. Mouse studies unraveled the bioactivity of Dex on NK cells. Indeed, Dex promoted an IL-15Rα- and NKG2D-dependent NK cell proliferation and activation respectively, resulting in anti-metastatic effects mediated by NK1.1+ cells. In humans, Dex express functional IL-15Rα which allow proliferation and IFNγ secretion by NK cells. In contrast to immature DC, human Dex harbor NKG2D ligands on their surface leading to a direct engagement of NKG2D and NK cell activation ex vivo. In our phase I clinical trial, we highlight the capacity of Dex based-vaccines to restore the number and NKG2D-dependent function of NK cells in 7/14 patients. Altogether, these data provide a mechanistic explanation on how Dex may stimulate non MHC restricted-anti-tumor effectors and induce tumor regression in vivo.
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